A deadly new “superbug” has recently emerged, with some infectious disease specialists calling it the most dangerous bug to hit the United States, Canada, and Europe in a decade.¹ The culprit is a new, more virulent epidemic strain of Clostridium difficile, so named because it was difficult to grow in the lab when first discovered.¹ This newly emerged strain of C. difficile (designated BI/NAP1) is distinct from the predominant strain that circulated in hospitals in the 1980s and 1990s. It produces 16 times more toxin A and 23 times more toxin B than the earlier strain. In addition, BI/NAP1 carries a gene for an additional virulence factor — a binary toxin similar to a toxin found in Clostridium perfringens.² Overall, the new strain of C. difficile causes disease that is more severe, more refractory to therapy, and subject to higher rates of relapse.^3,4

As the rates of BI/NAP1 increase in healthcare facilities across the nation, nurses are faced with the difficult challenge of keeping patients from becoming infected with this potentially severe, and sometimes even fatal, bacteria. Armed with knowledge about C. difficile’s transmission and adequate infection control measures, nurses can meet the challenge of helping fight this “difficult” pathogen.

C. difficile, a gram-positive, anaerobic, spore-forming bacteria, is the major cause of nosocomial diarrhea. The organism is clearly infectious and is transmitted via the fecal-oral route. It colonizes the intestinal tract of humans after normal intestinal flora have been disrupted by antibiotic therapy. Depending on host factors, the outcome of colonization can range from asymptomatic carriage to severe diarrhea, pseudomembranous colitis, toxic megacolon, leukemoid reactions, severe hypoalbuminemia, intestinal perforation, requirement for colectomy, shock, and death from secondary sepsis.^4,5,6

The number of cases of nosocomial C. difficile, as well as the proportion of cases with severe and fatal complications, has been increasing in hospitals across the United States and Canada.⁷ Each year in the United States, nearly 10% of patients hospitalized for more than two days (3 million patients) become infected with the pathogen at a cost estimated to exceed $1.1 billion.^5,8,9 Infections with C. difficile can lengthen a patient’s hospital stay by eight to 36 days with extra costs reaching as high as $10,000 per patient.^10,11 In many hospitals, C. difficile associated disease (CDAD) is a greater problem than methicillin-resistant Staphylococcus aureus (MRSA). In the United States, for example, the number of hospital discharge diagnoses of CDAD in 2001 to 2003 exceeded the estimated annual number of MRSA infections. In European hospitals, CDAD is now the most frequent nosocomial infection, exceeding infections caused by MRSA. In England, in 2003 CDAD resulted in twice as many deaths as MRSA.⁹

Who’s at risk

The normal intestinal bacterial flora in a healthy adult is resistant to colonization by C. difficile. However, when this normal flora is disrupted, resistance is impaired and exposure allows the pathogen to establish itself in the colon. Disruption of normal intestinal flora is most commonly caused by exposure to antibiotics, and more than 90% of C. difficile infections occur during or after antibiotic treatment.10 Almost all antibiotics now in use have been associated with C. difficile-associated diarrhea. This includes even metronidazole (Flagyl) and vancomycin (Vancocin), the primary drugs used to treat C. difficile-associated diarrhea. However, the antibiotics most frequently associated with C. difficile-associated diarrhea are those with broad-spectrum efficacy, such as third-generation cephalosporins — ceftazidime (Fortaz), ceftriaxone (Rocephin), ceftizoxime (Cefizox), ampicillin (Omnipen), amoxicillin (Amoxil), and clindamycin (Cleocin).¹² The newer fluoroquinolones may also be associated. Data from the recent outbreaks of C. difficile in Canadian hospitals suggest that the newly emerged virulent strain of this pathogen appeared after the introduction of fourth-generation fluoroquinolones, such as moxifloxacin (Avelox) and gatifloxacin (Tequin).⁷

Nearly all C. difficile infections in patients occur as a result of fecal-oral transmission by human vectors or by contact with a contaminated environment. The contamination occurs when patients infected with C. difficile-associated diarrhea or asymptomatic carriers of C. difficile shed the bacteria into their surroundings.¹³ Within four to five hours after being shed, C. difficile bacteria are able to change to a dormant form called a spore. In this spore form, C. difficile is highly resistant to cleaning and disinfection measures and can survive for months or even years on environmental surfaces.⁸ One study found spore contamination in 49% of rooms occupied by patients with diarrhea, 29% of rooms occupied by infected patients without diarrhea, and 8% of rooms occupied by culture-negative patients. Furthermore, the study found that 59% of healthcare workers, as well as 75% of physicians caring for infected patients, had hand cultures positive for C. difficile.^8,10 Patients have a high risk of infection or colonization when they are admitted to C. difficile-contaminated rooms and cared for by staff with C. difficile-contaminated hands.

In other studies, C. difficile spores have been cultured from bedside tables, handrails, bedside rails, call buttons, telephones, light switches, door handles, faucets, sinks, bathtubs, bedpans, toilets, IV pumps, wheelchairs, walkers, and equipment used to obtain vital signs or perform physical assessments. Spores have also been cultured from clothing and stethoscopes of healthcare workers caring for infected patients.^10,12

Other risk factors for C. difficile infection include:

• Age over 65
• Severe underlying illnesses
• GI surgery and procedures
• Feeding tubes, stool softeners, GI stimulants, antiperistaltic drugs, and enemas
• Antacids and proton pump inhibitors (acid suppressants used to treat peptic ulcers and esophageal reflux), such as lansoprazole (Prevacid), esomeprazole magnesium (Nexium), and omeprazole (Prilosec), and use of rectal thermometers.^7,10

How infection develops

Fewer than 3% of healthy adults in the United States and Europe carry C. difficile as part of their normal intestinal flora. When infections occur, virtually all are the result of ingesting C. difficile spores found in the hospital or by direct inoculation into the bowel via contaminated equipment, such as thermometers.¹⁰ Studies to determine the infective dose of C. difficile with antibiotic-treated animals indicate that ingesting as few as two spores may be enough to cause disease.¹³

Ingested spores of C. difficile are able to survive gastric acid and readily pass through the stomach. When the spores are exposed to bile acids in the small intestines, they germinate and produce two potent enterotoxins, toxin A and toxin B. Both toxins then seriously damage the lining of the colon (mucosa), resulting in inflammation, hemorrhage, and necrosis.⁵

About two-thirds of the patients who become colonized with C. difficile do not develop symptoms. For the one-third who do, symptoms can appear as early as one day after exposure to antibiotics or more than six weeks after antibiotic therapy has been completed.^3,5 For mild to moderate CDAD, the most common symptom is lower abdominal cramping pain without fever. In these cases, diarrhea is usually mild, with three or four loose, watery stools per day.

For moderate to severe cases of C. difficile-associated diarrhea (colitis without pseudomembrane formation), symptoms are profuse watery or mucoid, greenish, foul smelling diarrhea (10 to 15 stools per day) that may contain blood. In addition, abdominal distention, cramps, leukocytosis, fever, nausea, anorexia, and malaise often occur, and dehydration is common. Diarrhea can be unexpected and explosive, resulting in significant shedding of C. difficile spores into the environment.⁹

Very severe cases of CDAD (pseudomembranous colitis) present with the same clinical symptoms as severe colitis.¹² However, endoscopic examination of the colon in these cases shows inflamed mucosa studded with raised yellow and off-white plaques. The plaques often cover large portions of the mucosa and easily slough off, giving rise to the term “pseudomembrane.”

Fulminant pseudomembranous colitis with prolonged ileus, megacolon, and perforation occurs in 3% to 5% of patients and is associated with a high mortality rate, between 30% and 80%.⁸ Diarrhea may or may not occur due to paralytic ileus and an enlarged dilated colon (toxic megacolon). The only symptoms may be a high fever, severe lower or diffuse abdominal pain, tenderness, distention, and a moderate or marked leukocytosis. There may be signs and symptoms of bowel perforation with severe point tenderness and rebound tenderness. Abdominal rigidity, involuntary guarding, and reduced bowel sounds may also occur. For patients with fulminant pseudomembranous colitis, aggressive therapeutic interventions are necessary to prevent morbidity and mortality.¹³

Recurrent C. difficile-associated diarrhea occurs in 20% to 30% of successfully treated patients one week to two months after completion of treatment.⁸ Although the exact reasons for relapse are unclear, it may be because of a reinfection with C. difficile or to noneradicated spores in the colon. Both vancomycin and metronidazole can kill the vegetative (growing, reproducing) form of C. difficile, but neither kills the spores that can germinate after completion of treatment before the normal colonic flora are restored. Unfortunately, after treatment for the first relapse, nearly 65% of patients will have further recurrences.⁴ Approximately 50% of relapses, however, may be due to new C. difficile infections. Studies of patients with recurring CDAD who were thought to have relapsed indicate that 48% to 56% were infected with a different strain of C. difficile.³

To prevent infections and/or relapses, nonpathogenic bacteria called probiotics (Saccharomyces boulardii and Lactobacillus GG) are sometimes prescribed as an adjunct to antibiotic therapy to restore the colonization resistance of normal flora, and thereby prevent reinfection by C. difficile. Treatment with probiotics, however, has not made a statistically significant difference in rates of CDAD.³

Pinpointing C. difficile

Diagnosis of C. difficile is based on clinical symptoms supported by endoscopic findings and/or stool testing for the presence of the pathogen or toxins. C. difficile infection should be suspected in any patient with diarrhea who has received antibiotics in the last three months or whose diarrhea begins 72 hours after hospitalization.¹² The most common laboratory test in hospitals to diagnose C. difficile-associated disease is the enzyme-linked immunosorbent assay (ELISA), which checks for the presence of toxin A, toxin B, or both A and B. Laboratory tests of this type can provide accurate results in only a few hours. It should be noted that C. difficile toxin in a stool sample is very unstable. The toxin degrades at room temperature and may be undetectable within two hours if the specimen is not refrigerated.⁶

Which therapy is best?

CDAD will resolve itself in 20% to 25% of patients with mild disease without specific anti-C. difficile therapy — usually in two to three days by simply discontinuing the precipitating antibiotic.⁴ For patients with moderate to severe diarrhea/colitis, antibiotic therapy is needed to eradicate C. difficile. Currently, the antibiotics used for treatment are oral metronidazole (500 mg three times a day for 10 to 14 days) and oral vancomycin (125 mg four times a day for 10 to 14 days).⁸ The two drugs are equally effective. However, metronidazole is the drug of choice for most patients because it is less costly than vancomycin and is less likely to promote emergence of vancomycin-resistant enterococci (VRE). Metronidazole consistently achieves cure rates of 95%.⁸ Unfortunately, however, there have been some recent reports of C. difficile clinical isolates resistant to both metronidazole and vancomycin.³ Antidiarrheal agents, such as diphenoxylate hydrochloride and atropine sulfate (Lomotil) or loperimide (Imodium), and narcotic analgesics should be avoided because they may delay clearance of toxin from the colon. This can cause additional colon injury, or their use may cause ileus and toxic dilation.¹² Patients who develop fulminant colitis require admission to the ICU, where they may need an emergency colectomy because of severe ileus with dilated colon or impending perforation. The recommended procedure is a subtotal colectomy with ileostomy.¹³ Overall mortality for patients who need surgery is 30% to 80%.⁸

Fighting infection

Preventing infections with C. difficile in hospitals and long-term care facilities is a challenge for a number of reasons:

Over half of all hospitalized patients are treated with antibiotics, which makes them more susceptible to colonization or infection with C. difficile.¹¹ Asymptomatic colonized patients, who are fecal excretors (have C. difficile in their feces), are an important hidden reservoir of the bacteria. The bacteria/spores excreted by these patients can be transmitted throughout a facility on contaminated hands of healthcare workers and on shared patient-care equipment. Without testing all patients for C. difficile, there is no way to determine how many asymptomatic carriers are present in a hospital or what the colonization rate is. It is known that when patients become colonized, at least two-thirds do not develop clinical symptoms. What is not known is whether colonization is a temporary or permanent condition.¹² Currently, treatment of asymptomatic patients to eradicate carrier status is not recommended.¹⁰

Many common hospital disinfectants cannot kill the C. difficile spores found in rooms of colonized or infected patients. However, sodium hypochlorite (bleach) is effective for cleaning contaminated surfaces in patient rooms. Sodium hypochlorite, alkaline gluteraldehyde, or ethylene oxide are recommended for disinfecting patient care equipment and medical instruments.^3,10,12

The alcohol gel hand rubs (sanitizers) used in many hospitals to disinfect hands do not kill C. difficile spores. (Soap and water are recommended for handwashing when caring for infected/colonized patients. Healthcare workers should also wear clean nonsterile gloves when caring for patients and when touching patient environments).³

Many U.S. hospitals have had to cut costs to remain solvent. One measure has been to reduce cleaning staff, and in the last decade, hospital housekeeping staffs have been cut by 25%.¹⁴ At the same time, nursing workloads have increased because of a severe nursing shortage. The combination of fewer nurses and fewer housekeeping staff has led to less time for cleaning contaminated rooms and for handwashing.¹⁵

The following precautions should be taken to prevent patient-to-patient spread of C. difficile.¹⁶

• Antibiotics associated with high rates of CDAD should be avoided.
• All healthcare workers, including housekeeping, dietary, and maintenance, should receive information about the transmission of C. difficile and precautions to interrupt transmission.
• As soon as CDAD is suspected or identified, patients should be placed in a private room with a private bathroom. If private rooms are not available, patients can be placed in rooms with other patients with CDAD (cohorted). If bathrooms are shared with noninfected patients, an individual commode chair should be used.
• Signs or placards indicating precautions to be used should be posted on the door of any room with a suspected or confirmed CDAD patient.
• Healthcare workers should use gowns and gloves for all contact with colonized or infected patients. Gowns and gloves should be put on before entering the room of infected or colonized patients and removed upon exiting. This prevents healthcare workers from carrying the pathogen on their clothes to other patients.
• Hands should be washed with soap and water for at least 15 seconds to physically remove C. difficile spores. Alcohol-based hand rubs are not effective against spore-forming bacteria and should not be used as the primary method of hand cleaning.
• Disposable or dedicated equipment should be used for each suspected or confirmed CDAD patient. Patient-care equipment such as blood pressure cuffs, stethoscopes, and thermometers should remain in the patient’s room and not shared with other patients. Electronic rectal thermometers have been implicated in CDAD outbreaks and should not be used.
• Patient rooms and medical equipment should receive careful cleaning/disinfection with an agent capable of destroying C. difficile and its spores. Hypochlorite-based disinfectants or household bleach (1/4 cup household bleach to 1 gallon of water) can be used to disinfect environmental surfaces. Warning: Never mix chlorine bleach solution with other cleaning solutions or detergents containing ammonia, because this may produce highly toxic vapors.
• Rooms should be terminal cleaned when a CDAD patient is discharged. Privacy curtains should be taken down and sent for laundering, and all disposable items that cannot be disinfected should be thrown away.¹⁶

Because of the increased incidence and severity of CDAD, the Centers for Disease Control and Prevention (CDC) has recommended direct surveillance and reporting of healthcare-associated CDAD. To implement surveillance, the following definitions have been developed:

Case definition for CDAD

Diarrhea: Unformed stools that take the shape of the specimen collection container — or toxic megacolon — abnormal dilation of the large intestine documented radiologically, AND

• Stool sample — positive assay for C. difficile toxin A and/or B, or a positive stool culture with a toxin-producing C. difficile organism;
• Pseudomembranous colitis is seen during endoscopic examination or surgery; and
• Pseudomembranous colitis is seen during histopathological examination.^2,3

Definition of CDAD recurrence

• Two episodes of CDAD in the same patient that occur less than eight weeks apart are considered a relapse. It is not possible in clinical practice to determine whether the second occurrence is a relapse with the same strain or a reinfection with a different strain.^2,3

Definition of a case of severe CDAD

Severe CDAD: any patient who meets any of the following criteria within 30 days after CDAD diagnosis.

• History of admission to an ICU for complications associated with CDAD (e.g., shock requiring vasopressor therapy)
• Surgery (colectomy) for toxic megacolon, perforation, or refractory colitis
• Death caused by CDAD within 30 days after symptom onset (e.g., listed on death certificate or recorded in medical record by clinician caring for patient.)^2,3

Hospitals across the country need to prepare for this new, more virulent strain of C. difficile. Nurses play a vital role in preventing transmission of this pathogen to their patients. They can do this by paying careful attention to infection control measures and by ensuring that everyone having contact with infected patients follows contact (barrier) precautions.